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Sökning: onr:"swepub:oai:DiVA.org:su-170819" > Disruption of the E...

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FältnamnIndikatorerMetadata
00008899naa a2200877 4500
001oai:DiVA.org:su-170819
003SwePub
008190730s2019 | |||||||||||000 ||eng|
009oai:lup.lub.lu.se:dd004f7d-31a5-4193-ac94-3f225200bc62
009oai:DiVA.org:liu-158947
009oai:prod.swepub.kib.ki.se:141247867
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1708192 URI
0247 a https://doi.org/10.1161/ATVBAHA.119.3123882 DOI
0247 a https://lup.lub.lu.se/record/dd004f7d-31a5-4193-ac94-3f225200bc622 URI
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-1589472 URI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1412478672 URI
040 a (SwePub)sud (SwePub)lud (SwePub)liud (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Jensen, Lasseu Linköpings universitet,Linköping University,Avdelningen för kardiovaskulär medicin,Medicinska fakulteten,Region Östergötland, Klinisk farmakologi4 aut0 (Swepub:liu)larje86
2451 0a Disruption of the Extracellular Matrix Progressively Impairs Central Nervous System Vascular Maturation Downstream of beta-Catenin Signaling
264 1b LIPPINCOTT WILLIAMS & WILKINS,c 2019
338 a print2 rdacarrier
500 a Funding Agencies|Cancerfonden [CAN 2010/679]; Karolinska Funding for Doctorial Studies; Swedish Society for Medical Research; Jeanssons Stiftelser; Swedish Research Council; H2020-MSCA-RISE (3D-NEONET); Johnson Johnson [K240001043]; Marie Curie FP7 people initiative Fellowship [626544]; National Institutes of Health [AR070748, AR53890]; Swedish Brain Foundation; Tore Nilsons Stiftelse; Tornspiran; Lars Hiertas Stiftelse; Jane Foundation; Dan Olsson Foundation; Samariten and Bergvalls Stiftelse
520 a Objective- The Wnt/beta-catenin pathway orchestrates development of the blood-brain barrier, but the downstream mechanisms involved at different developmental windows and in different central nervous system (CNS) tissues have remained elusive. Approach and Results- Here, we create a new mouse model allowing spatiotemporal investigations of Wnt/beta-catenin signaling by induced overexpression of Axin1, an inhibitor of beta-catenin signaling, specifically in endothelial cells (Axin1(iEC)-(OE)). AOE (Axin1 overexpression) in Axin1(iEC)-(OE) mice at stages following the initial vascular invasion of the CNS did not impair angiogenesis but led to premature vascular regression followed by progressive dilation and inhibition of vascular maturation resulting in forebrain-specific hemorrhage 4 days post-AOE. Analysis of the temporal Wnt/beta-catenin driven CNS vascular development in zebrafish also suggested that Axin1(iEC)-(OE) led to CNS vascular regression and impaired maturation but not inhibition of ongoing angiogenesis within the CNS. Transcriptomic profiling of isolated, beta-catenin signaling-deficient endothelial cells during early blood-brain barrier-development (E11.5) revealed ECM (extracellular matrix) proteins as one of the most severely deregulated clusters. Among the 20 genes constituting the forebrain endothelial cell-specific response signature, 8 (Adamtsl2, Apod, Ctsw, Htra3, Pglyrp1, Spock2, Ttyh2, and Wfdc1) encoded bona fide ECM proteins. This specific beta-catenin-responsive ECM signature was also repressed in Axin1(iEC)-(OE) and endothelial cell-specific beta-catenin-knockout mice (Ctnnb1-KOiEC) during initial blood-brain barrier maturation (E14.5), consistent with an important role of Wnt/beta-catenin signaling in orchestrating the development of the forebrain vascular ECM. Conclusions- These results suggest a novel mechanism of establishing a CNS endothelium-specific ECM signature downstream of Wnt-beta-catenin that impact spatiotemporally on blood-brain barrier differentiation during forebrain vessel development.
650 7a NATURVETENSKAPx Biologi0 (SwePub)1062 hsv//swe
650 7a NATURAL SCIENCESx Biological Sciences0 (SwePub)1062 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Cell- och molekylärbiologi0 (SwePub)301082 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Cell and Molecular Biology0 (SwePub)301082 hsv//eng
653 a basement membrane
653 a blood-brain barrier
653 a central nervous system
653 a embryonic development
653 a endothelial cells
653 a extracellular matrix
653 a vasculature
653 a basement membrane
653 a blood-brain barrier
653 a central nervous system
653 a embryonic development
653 a endothelial cells
653 a extracellular matrix
653 a vasculature
7001 a Hot, Belmau Karolinska Institute,Ludwig Institute for Cancer Research, Stockholm branch,Karolinska Inst, Sweden; Ludwig Inst Canc Res Ltd, Sweden4 aut
7001 a Ramsköld, Danielu Karolinska Institutet,Karolinska Institute,Ludwig Institute for Cancer Research, Stockholm branch,Karolinska Inst, Sweden; Ludwig Inst Canc Res Ltd, Sweden4 aut
7001 a Germano, Raoul F. V.u Université Libre de Bruxelles (ULB),Univ Libre Bruxelles, Belgium4 aut
7001 a Yokota, Chikau Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik,Ludwig Institute for Cancer Research Ltd, Sweden,Ludwig Institute for Cancer Research, Stockholm branch,Ludwig Inst Canc Res Ltd, Sweden; Stockholm Univ, Sweden4 aut0 (Swepub:su)cyoka
7001 a Giatrellis, Sarantisu Karolinska Institutet,Karolinska Institute,Karolinska Inst, Sweden4 aut
7001 a Lauschke, Volker M.u Karolinska Institutet,Karolinska Institute,Karolinska Inst, Sweden4 aut
7001 a Hubmacher, Dirku Icahn School of Medicine at Mount Sinai,Icahn Sch Med Mt Sinai, NY 10029 USA4 aut
7001 a Li, Minerva X.u Lund University,Lunds universitet,LUBIN Lab- Lunds laboratorium för neurokirurgisk hjärnskadeforskning,Forskargrupper vid Lunds universitet,LUBIN Lab- Lund Brain Injury laboratory for Neurosurgical research,Lund University Research Groups,Ludwig Institute for Cancer Research, Stockholm branch,Ludwig Inst Canc Res Ltd, Sweden; Lund Univ, Sweden4 aut0 (Swepub:lu)med-mvl
7001 a Hupe, Mikeu Julius Maximilian University of Würzburg,Ludwig Institute for Cancer Research, Stockholm branch,Ludwig Inst Canc Res Ltd, Sweden; Univ Wurzburg, Germany4 aut
7001 a Arnold, Thomas D.u University of California, San Francisco,Univ Calif San Francisco, CA 94143 USA4 aut
7001 a Sandberg, Rickardu Karolinska Institutet,Karolinska Institute,Ludwig Institute for Cancer Research, Stockholm branch,Karolinska Inst, Sweden; Ludwig Inst Canc Res Ltd, Sweden4 aut
7001 a Frisén, Jonasu Karolinska Institutet,Karolinska Institute,Karolinska Inst, Sweden4 aut
7001 a Trusohamn, Martau Karolinska Institute,Karolinska Inst, Sweden4 aut
7001 a Martowicz, Agnieszkau Karolinska Institute,Karolinska Inst, Sweden4 aut
7001 a Wisniewska-Kruk, Joannau Karolinska Institute,Karolinska Inst, Sweden4 aut
7001 a Nyqvist, Danielu Karolinska Institutet,Karolinska Institute,Karolinska Inst, Sweden4 aut
7001 a Adams, Ralf H.u University of Münster,Univ Munster, Germany4 aut
7001 a Apte, Suneel S.u Cleveland Clinic Foundation,Cleveland Clin Fdn, OH 44195 USA4 aut
7001 a Vanhollebeke, Benoitu Walloon Excellence in Life Sciences and Biotechnology,Université Libre de Bruxelles (ULB),Univ Libre Bruxelles, Belgium; Walloon Excellence Life Sci and Biotechnol WELBIO, Belgium4 aut
7001 a Stenman, Jan M.u Ludwig Institute for Cancer Research, Stockholm branch,Ludwig Inst Canc Res Ltd, Sweden4 aut
7001 a Kele, Juliannau Karolinska Institutet,Karolinska Institute,Ludwig Institute for Cancer Research, Stockholm branch,Karolinska Inst, Sweden; Ludwig Inst Canc Res Ltd, Sweden4 aut
7102 a Linköping Universityb Avdelningen för kardiovaskulär medicin4 org
7730 t Arteriosclerosis, Thrombosis and Vascular Biologyd : LIPPINCOTT WILLIAMS & WILKINSg 39:7, s. 1432-1447q 39:7<1432-1447x 1079-5642x 1524-4636
8564 u https://doi.org/10.1161/ATVBAHA.119.312388y Fulltext
8564 u http://dx.doi.org/10.1161/ATVBAHA.119.312388x freey FULLTEXT
8564 u https://liu.diva-portal.org/smash/get/diva2:1338183/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-170819
8564 8u https://doi.org/10.1161/ATVBAHA.119.312388
8564 8u https://lup.lub.lu.se/record/dd004f7d-31a5-4193-ac94-3f225200bc62
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-158947
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:141247867

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